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Repairing Damaged Tissues

Decades of research into nerve physiology, MS tissue damage and the biology of glial cells – the numerous brain cells that support nerve cells – have laid the groundwork for finding ways to restore normal function in individuals with MS.

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Nervous System Repair – Reversing Damage to Regain Function

Repairing the nervous system, in particular myelin, the coating that surrounds and protects axons (nerve wires) and which is damaged by MS, was just a dream just a few years ago. Today it holds significant promise as a strategy to restore the function that MS has taken from people; and reducing or stopping MS progression. This remarkable progress is due to the National MS Society’s comprehensive efforts and multi-million dollar research investments.

We are at a pivotal moment in time where breakthrough solutions can change the world for everyone with MS. Among the approaches being taken are:
• Clinical trials to stimulate the natural capacity of the brain to repair itself.
• Tests of the ability of stem cells to treat MS damage.
• Finding ways to protect the nervous system to allow natural myelin repair to occur.
• Developing better ways to track successful repair.

This exciting research area has been gaining momentum since the Society’s 2005 global initiative funded four collaborative teams who were focused on nervous system protection and repair. Over five years, the teams engaged more than 100 investigators, produced over 180 research papers, identified new therapeutic targets and launched clinical trials to test neuroprotective strategies.

Promoting natural capacity for repair

Research shows that the brain does repair myelin to some extent, but myelin repair may stall. While we don’t fully understand why repair fails in MS, early clinical trials are now underway to test their ability to stimulate myelin repair. The Society is supporting research looking at key molecules that are important to the cells that make myelin (oligodendrocytes) and that may serve as targets for promoting myelin repair. Promising solutions to restore function are now at our fingertips:
• In a small, phase II clinical trial, the oral antihistamine clemastine modestly improved the transmission of electrical signals in the optic nerve in participants with MS who had optic nerve damage. Clemastine was identified as having possible myelin-repairing properties through innovative preclinical research conducted by National MS Society-funded Jonah Chan, PhD, who went on to become first recipient of the Barancik Prize for Innovation in MS Research for this pioneering work.
• Several Society-supported commercial research initiatives are exploring ways to enhance the ability of oligodendrocytes to proliferate in areas of myelin damage to facilitate repair. For example, we’re supporting New York University researchers, who found that by blocking a molecule present in specific stem cells, they were able to stimulate myelin repair and some recovery in mice with an MS-like disease.

Stem Cell Therapy

There is exciting progress being made through innovative research related to the potential of many types of stem cells for both slowing MS disease activity and for repairing damage to the nervous system. With the urgent need for more effective treatments for MS, particularly for those with more progressive forms of the disease, we believe that the potential of all types of cell therapies must be explored. The Society is currently supporting 12 research projects exploring various types of stem cells, including cells derived from bone marrow, fat and skin, and has supported 68 stem cell studies over the past 10 years.

Protecting the nervous system

To stop further damage and allow natural myelin repair to occur, the Society funds clinical trials of potential therapies that will protect the nervous system. For example:
• Ibudilast – a repurposed drug with protective potential for progressive forms of MS (funded with the Cleveland Clinic Foundation and National Institutes of Health’s NeuroNEXT Network). Ibudilast was well tolerated and significantly slowed the rate of brain atrophy compared to placebo.
• Lipoic acid – antioxidant may help block nerve fiber damage in MS
• Phenytoin – A trial funded in part by the MS Societies of the U.S. and the U.K., showed that people with optic neuritis, an inflammation of the optic nerve and often the first symptom of MS, who were taking this epilepsy treatment had 30% less damage to the nerve fiber layer compared to those who received placebo. The results need confirmation in a larger study
• The MS-SMART trial which is testing three therapies that may have nerve-protecting properties in secondary-progressive MS (funded in collaboration with the United Kingdom MS Society)

Tracking repair

The Society fuels research to find ways to detect whether the nervous system is being repaired or protected by therapies in future clinical trials. Approaches include:
• Non-conventional brain imaging and scanning nerves at the back of the eye
• Biomarkers in the blood or spinal fluid – which could be “footprints” that indirectly indicate the success of a repair therapy
• Better clinical readouts – called outcome measurements -- that can determine whether a repair or protection therapy is working, without waiting years to watch the disease course

Finding Repair Solutions

Achieving success in the Society’s priority area of nervous system repair would provide life-changing advances for people with MS. It could allow us to restore neurological function for people with all types of MS, including progressive forms of the disease.